Homozygous Southeast Asian ovalocytosis is a severe dyserythropoietic anemia associated with distal renal tubular acidosis

Picard, Véronique; Proust, Alexis; Eveillard, Marion; Flatt, Joanna F.; Couec, Marie‐Laure; Caillaux, Gaêlle; Fénéant-Thibault, Madeleine; Finkelstein, Arie; Raphaël, Martine; Delaunay, Jean; Bruce, Lesley J.; Pissard, Serge; Thomas, Caroline

doi:10.1182/blood-2014-01-548149

Cited by 35 publications

(33 citation statements)

References 11 publications

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“…Until very recently, SAO‐AE1 homozygotes had not been observed, presumably as the genotype is seriously deleterious in utero . Consistent with this notion was the recent first report of a child homozygous for the SAO allele, who was prematurely born, manifested severe anemia (treatable by transfusion), and developed dRTA . dRTA is common among SAO individuals, as SAO‐AE1 is not functional in anion exchange, and thus, mutation of their second AE1 allele leaves them with greatly compromised AE1 function.…”

Section: Introductionmentioning

confidence: 74%

Bicarbonate transport in health and disease

Kumari

Casey

2014

IUBMB Life

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Bicarbonate (HCO 3 2 ) has a central place in human physiology as the waste product of mitochondrial energy production and for its role in pH buffering throughout the body. Because bicarbonate is impermeable to membranes, bicarbonate transport proteins are necessary to enable control of bicarbonate levels across membranes. In humans, 14 bicarbonate transport proteins, members of the SLC4 and SLC26 families, function by differing transport mechanisms. In addition, some anion channels and ZIP metal transporters contribute to bicarbonate movement across membranes. Defective bicarbonate transport leads to diseases, including systemic acidosis, brain dysfunction, kidney stones, and hypertension. Altered expression levels of bicarbonate transporters in patients with breast, colon, and lung cancer suggest an important role of these transporters in cancer. V C 2014 IUBMB Life, 66(9): [596][597][598][599][600][601][602][603][604][605][606][607][608][609][610][611][612][613][614][615] 2014

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Section: Introductionmentioning

confidence: 74%

Bicarbonate transport in health and disease

Kumari

Casey

2014

IUBMB Life

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“…Complete loss of band 3 was hitherto reported in only one other homozygous case with HS; the bone marrow was not examined in this case, so it is not known whether there were dyserythropoietic abnormalities . Conversely, dyserythropoiesis was observed in one patient with homozygous SAO in which SAO band 3 was still present . Although the essential functional role of band 3 in erythroid and kidney cells is well established, it still remains unclear how the loss or instability of band 3 may or may not affect immature erythroblasts.…”

Section: Resultsmentioning

confidence: 98%

“…Preparation of RBC membranes, SDS-PAGE, Coomassie staining and immunoblotting were performed as described. 11 Confocal microscopic imaging of peripheral blood samples was performed as described 4 and detailed in the corresponding figure legend. (rs13306780) in intron 17, which were also present in heterozygous form in both parents and siblings (Fig.…”

Section: Protein Analysis and Confocal Microscopymentioning

confidence: 99%

“…However, mutations causing severe loss of anion exchange function in red cells are rare and usually lethal. Thus, only 15 homozygous individuals from seven families with severe forms of hemolytic anemia with and without dyserythropoiesis and complete dRTA have been reported so far: a Comorian patient with South‐east Asian ovalocytosis (SAO) and an exon 11 p.400‐408 deletion, an infant with spherocytosis and an exon 13 p.V488M COIMBRA mutation, an Italian patient with spherocytosis and a single base substitution NC_000017.11:g.44262850T>C NEAPOLIS in the donor splice site of intron 2, an Algerian patient with spherocytosis and an exon 16 p.S667F COURCOURONNES mutation, and 11 individuals with an exon 19 p.Ala858Asp mutation: two Indian patients with ovalocytosis, Indian twins of nonconsanguineous parents with spherocytosis, and seven Omani Arab members of a consanguineous family with compensated dyserythropoietic ovalocytosis …”

Section: Introductionmentioning

confidence: 99%

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Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

Kager

Bruce

Zeitlhofer³

et al. 2016

Pediatric Blood & Cancer

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We describe the second patient with anionic exchanger 1/band 3 null phenotype (band 3 null ), which was caused by a novel nonsense mutation c.1430C>A (p.Ser477X) in exon 12 of SLC4A1. We also update on the previous band 3 null patient, thereby elucidating the physiological implications of total loss of AE1/band 3. Besides transfusion-dependent severe hemolytic anemia and complete distal renal tubular acidosis, dyserythropoiesis was identified in the band 3 null patient, suggesting a role for band 3 in erythropoiesis. Moreover, we also, for the first time, report that long-term survival is possible in band 3 null patients.

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“…This patient showed severe phenotype with intrauterine transfusions, transfusion dependent anemia and distal renal tubular acidosis due to the loss of band 3, which is also expressed in the kidneys. 28 …”

Section: Southeast Asian Ovalocytosismentioning

confidence: 99%

New insights on hereditary erythrocyte membrane defects

et al. 2016

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© Ferrata Storti Foundationmary role in the removal of aged RBCs. In order to perform these journeys RBCs must possess and maintain a significant deformability. The main author of this property is certainly the membrane, that ensures both mechanical stability and deformability. After the first proposed model of the RBC membrane skeleton 36 years ago, 1 containing the core elements of the modern model, many additional proteins have been discovered during the intervening decades, and their structures and interactions have been defined. RBC membrane structure has been extensively covered by excellent reviews.2,3 Herein we summarize the main concepts. RBC membrane is composed by a fluid double layer of lipids in which approximately 20 major proteins and at least 850 minor ones are embedded. 4 The membrane is attached to an intracellular cytoskeleton by protein-protein and lipid-protein interactions that confer the erythrocyte shape, stability and deformability. The transmembrane proteins have mainly a transporter function. However, several of these also have a structural function, usually performed by an intracytoplasmic domain interacting with cytoskeletal proteins.The lipid bilayer acts as a barrier for the retention of cations and anions within the red cells, while it allows water molecules to pass through freely. Human erythrocytes have high intracellular K + and low intracellular Na + contents when compared with the corresponding ion concentrations in the plasma. The maintenance of this cation gradient between the cell and its environment involves a passive outward movement of K + , which is pumped back by the action of an ATP-dependent Na + /K + pump in exchange for Na+ ions. This protein belongs to a class of transmembrane proteins with a transport function (Figure 1). The third and more important component of the RBC membrane is the cytoskeleton, a protein network that laminates the inner surface of the membrane. Spectrin aand β-chains, proteins 4.1, or 4.1R, and actin are the main components of this skeleton, maintaining the biconcave shape of the RBC. These components are connected to each other in two protein complexes; ankyrin and protein 4.1 complex. The former is composed by band 3 tetramers, Rh, RhAG, CD47, glycophorin A and protein 4.2. Whereas the protein 4.1 complex is composed by band 3 dimers binding adducins a-and β-, glycophorin C, GLUT1 and stomatin (Figure 1). The ends of spectrin tetramers converge toward a protein 4.1 complex (junctional complex). Electron microscopy (EM) shows that this latter links the tail of six spectrin tetramers, forming a pseudo-hexagonal arrangement. 5Spectrin tetramers include anion transporters (band 3 or chloride/bicarbonate exchange). The capability of these transporters to form aggregates could define the half-life of RBCs, causing antibody binding and removal by the spleen. Defects that interrupt this vertical structure (spectrin-actin interaction) underlie the biochemical and molecular basis of hereditary spherocytosis (HS), whereas defects in horizo...

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Homozygous Southeast Asian ovalocytosis is a severe dyserythropoietic anemia associated with distal renal tubular acidosis

Cited by 35 publications

References 11 publications

Bicarbonate transport in health and disease

Bicarbonate transport in health and disease

Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

New insights on hereditary erythrocyte membrane defects

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Homozygous Southeast Asian ovalocytosis is a severe dyserythropoietic anemia associated with distal renal tubular acidosis

Cited by 35 publications

References 11 publications

Bicarbonate transport in health and disease

Bicarbonate transport in health and disease

Band 3 nullVIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis

New insights on hereditary erythrocyte membrane defects

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Band 3 null^VIENNA, a novel homozygous SLC4A1 p.Ser477X variant causing severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis